In the past few years, numerous proteins have been identified as containing a stretch of about 75 amino acids which are homologous to an abundant non-histone chromosomal protein HMG-1. These proteins bind DNA and bends it on binding or bind preferentially bind to bent DNA. Several of these proteins have been implicated in numerous nuclear functions including transcription, replication, and chromatin structure as well as transcription regulation in mitochondria resulting, in some cases, in such phenotypes as sex and mating type determination. Examples of these proteins are UBF, an RNA polymerase I transcription factor; SRY, the mammalian testis-determining factor; LEF-1/TCF1a, the lymphoid enhancer binding factor; and T160, a V-(D)-J recombinase which is very similar to SSRP1, a structure specific recognition protein that binds cisplatin- modified DNA. In addition, there are several yeast proteins involved in mating type determinations and sexual development. We are compiling and maintaining a database of the HMG-1 box family of proteins and are analyzing the sequences to determine the phylogeny between these functionally widely-diverse proteins. Recently, the 3D structure of an HMG-1 box from rat HMG-1 has been determined by two dimensional NMR spectroscopy (Weir, et al. 1993). We plan to use this structure to improve our alignment and to model other members of the family. Other DNA-binding proteins are being analyzed in a similar way.